Prior investigations have shown that a neuromuscular mechanism exists within the intramural portion of the smooth muscle segment of the esophagus which may be responsible for the peristaltic events seen in the circular and longitudinal muscle layers during the act of swallowing. The overall objective of this proposal is to pharmacologically characterize the intramural innervation of esophageal longitudinal and circular smooth muscle layers and determine what roles specific components of this innervation play in the peripheral mechanism of esophageal peristalsis. Specifically, this proposal involves the use of in vitro and in vivo techniques to study circular and longitudinal esophageal smooth muscle contractions in response to nerve stimulation. In vitro studies will involve transmural stimulation of esophageal muscle strips and in vivo studies will involve vagal stimulation or swallow-induced muscle contractions. The effects of various antagonists and agonists on these nerve-mediated muscle contractions will be determined so as to identify the various components of innervation. The results of these studies will provide a better understanding of the intramural neuromuscular mechanism involved in esophageal peristalsis. This should lead to an increased understanding of the pathophysiology of esophagel disorders and perhaps a more rational therapy for such disorders as diffuse esophageal spasm and achalasia. The candidate, under the sponsorship of Dr. Raj K. Goyal, was the recipient of an individual National Research Service Award to study the peripheral mechanisms of esophageal peristalsis. This work has resulted in several important publications concerning esophageal peristalsis. The candidate in the present proposal wishes to extend these studies concerning the mechanisms of esophageal peristalsis as he progresses toward becoming an independent investigator. The sponsor, Dr. Raj K. Goyal, is Professor of Medicine at Harvard Medical School and Chief of Gastroenterology at Beth Israel Hospital and is an acknowledged leader in the area of gastrointestinal motility. Dr. Goyal's sponsorship, as well as surrounding investigators at Beth Israel Hospital and Harvard Medical School should provide an excellent environment for the candidate's studies and development.